Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

Limbic activity in antipsychotic naïve first-episode psychotic subjects during facial emotion discrimination.

The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment and clinical improvement, the voxel-wise approach showed a significant increase in activity in lingual gyrus and calcarine fissure in the group of patients. The regions of interest analysis showed an increase in amygdala activity during anger discrimination also in the group of patients. The results suggest a state-dependent model depicting a flattened and aberrant response of amygdala to emotion discrimination that could explain the seemingly contradictory previous findings of hypo- and hyper-amygdala activation.

Relapse of first-episode schizophrenia patients and neurocognitive impairment: The role of dopaminergic and anticholinergic burden.

BACKGROUND: The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up. METHODS: Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, after >2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions. RESULTS: Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden. CONCLUSIONS: The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.

A Randomized Trial of Deep Brain Stimulation to the Subcallosal Cingulate and Nucleus Accumbens in Patients with Treatment-Refractory, Chronic, and Severe Anorexia Nervosa: Initial Results at 6 Months of Follow Up.

BACKGROUND: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). METHODS: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). RESULTS: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. CONCLUSION: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed.

Predictors of Relapse and Functioning in First-Episode Psychosis: A Two-Year Follow-Up Study.

OBJECTIVE: First-episode psychosis has an annual incidence rate of 24.6 to 40.9 per 100,000 population, and most individuals develop chronic disorders, such as schizophrenia or affective psychosis. The first two to five years are thought to be key determinants of long-term functional and clinical prognosis. This study aimed to determine the two-year course of illness in first-episode psychosis, including diagnosis, relapse, and functioning and factors related to these variables. METHODS: A total of 140 patients who experienced a first episode of psychosis were recruited and evaluated between 2008 and 2012 in a first-episode psychosis program in Barcelona, Spain. Regression models were used to determine factors predicting relapse and functioning. RESULTS: A general trend was noted toward improved functioning and less severe psychotic symptoms. However, after two years, one-third of the patients had a diagnosis of schizophrenia and more than 40% had a diagnosis of affective psychosis. Rates of relapse were 31% after one year and 43% at two years. Cannabis use after illness onset and poor insight were the best predictors of relapse. Being male and severity of negative symptoms at baseline predicted worse functioning at two years. CONCLUSIONS: Patients with first-episode psychosis were found to have high relapse rates during the first years after illness onset. Further studies evaluating treatment strategies focused on reducing cannabis use and improving insight in first-episode psychosis should be encouraged.

Analysis of polymorphisms at the tumor suppressor gene p53 (TP53) in contributing to the risk for schizophrenia and its associated neurocognitive deficits.

Owing to the role of the nuclear phosphoprotein p53 in the regulation of neurodegeneration and neurodevelopmental processes, some authors have suggested TP53 as a candidate gene for schizophrenia and/or the neurocognitive deficits commonly observed in these patients. In the present study we have analyzed two polymorphisms (Pro72Arg and 16 bp insertion) located on the TP53 gene in order to investigate their role in the risk of developing schizophrenia and their effect on the neurocognitive profile of these patients in the context of an association study. The distribution of genotypes, alleles and haplotypes did not differ between cases and controls. Additionally, we did not detect any influence of this genetic variability in the neurocognitive functions of schizophrenic patients. Our findings suggest that the analyzed variability of the TP53 gene does not influence (i) the risk of suffering from schizophrenia and (ii) the deficits in the neurocognitive profile of these patients.

Identification of two risk haplotypes for schizophrenia and bipolar disorder in the synaptic vesicle monoamine transporter gene (SVMT).

The synaptic vesicular monoamine transporter (SVMT) plays a key role in monoaminergic neurotransmission determining the size of neurotransmitter vesicular pools available for exocytotic release. Recently, several lines of evidence have suggested that altered functions of SVMT may be involved in the pathogenesis of certain neuropsychiatric diseases, including psychotic and mood disorders. In the present study, we tested the potential involvement of SVMT gene variants in the etiology of schizophrenia and bipolar disorder. Five different SNPs (T440G, C1368T, T2666C, A2683C, and A745G) were included in the analysis covering a region of about 35 kb along the SVMT gene. Analyses were performed in a case-control sample consisting of 88 bipolar patients, 107 subjects with schizophrenia, and 164 controls. Two risk haplotypes for both schizophrenia and bipolar disorder in SVMT gene were identified. Particularly, 2666T-2683A-745G (TAG) and 2666C-2683C-745A (CCA) combinations were significantly more frequent in both bipolar and schizophrenic patients than in controls. UNPHASED package estimated haplotype effects for all patients yielded relative risks of 4.1 (95%CI: 1.83-9.21) for TAG combination and 2.336 (95%CI: 1.28-4.26) for CCA haplotype. Conversely, 2666T-2683C-745A (TCA) and 2666C-2683A-745G (CAG) haplotypes seemed to protect against these mental disorders, since the estimated frequency in control chromosomes was 12% whilst such haplotypes were not observed in any bipolar or schizophrenic subject (P < 0.0000). Our results strongly suggest that SVMT gene or certain regions of it may constitute a genetic substrate of susceptibility for both schizophrenia and bipolar disorder.